DESCRIPTION: The goal of this proposal is to further characterize IL-3 signal transduction with focus on activation of RAF-1, which leads to hematopoietic proliferation, and BCL-2-alpha which leads to inhibition of apoptosis. There are two specific aims. Specific Aim 1 is to determine the mechanism and functional significance of IL-3 mediated phosphorylation and activation of RAF-1. Subaims will be to determine if protein kinase C-alpha is the direct activator of RAF-1, to determine which sites on RAF-1 which are phosphorylated are important for activation, to determine the role of IL-3 mediated RAF-1 tyrosine phosphorylation and to determine how RAF-1 is activated in the complex with MEK. The second specific aim is to determine the mechanism, site, and functional significance of IL-3 induced BCL-2 phosphorylation. Subaims are to determine whether PKC-alpha phosphorylates BCL-2 alpha directly, to determine how phosphorylation affects BCL-2 function, and to determine whether RAF-1 and the BCL-2 interact, and if BCL-2 is a target of RAF-1.